The major objective of this research is to determine the relationships between brain blood flow, brain hypoxia and control of breathing in unanesthetized goats. Three models of brain hypoxia (inhalation of carbon monoxide, hypoxic hypoxia in peripherally chemodenervated animals and reduction of brain flow) will be examined. Levels of brain hypoxia will be assessed in terms of oxygenation of arterial blood, oxygen delivery to the brain, cerebral venous gas tensions, brain uptake of oxygen and glucose and brain production of lactate. Responses will be assessed in terms of minute ventilation and its components (frequency, tidal volume, inspiratory time) and with regard to effects of brain hypoxia on other elements of ventilatory control such as the response to mechanical loads. In additional studies ventilation, brain blood flow and cerebral venous gas tensions will be monitored simultaneously in order to assess the role of brain blood flow in the ventilatory response to various drugs, such as narcotic agents. Related studies are proposed to examine the relationship between ventilatory and circulatory responses to hypoxia in neonatal lambs, the effects of sleep on the relationships between ventilatory responses to hypoxia, hypercapnia and mechanical loading in cats, and the effects of prolonged, severe anemia on the ventilatory response to hypoxia.